Current techniques for protein detection, analysis and quantification include, e.g., two-dimensional gel electro-phoresis combined with mass spectroscopy, micro-capillary electrokinetic separation techniques with fluorescent read-out, micro-array analogs to DNA chip technology, and others like plasmon-resonance or quartz microbalance. In present micro-array approaches the underlying “chip” mostly consists of a surface functionalized plain glass substrate without any intrinsic function, detection hence relies solely on fluorescent labeling.
A common approach using silicon structures for the detection of biomolecular interactions is the use of capacitive measurements (Berggren et al., Electroanalysis 2001). Their usability is hampered by the need of highly insulating organic layers. Light addressable potentiometric sensors (LAPs) have also been proposed as a detection scheme (George et al., Sensors and Acuators, 2000). However, these approaches in general lack the sensitivity and universality. Also, standard FET structures were proposed for the use of biosensors, but lacked the necessary sensitivity as well (e.g. Schöning and Lüth, 2001). A further approach is the detection by means of mechanical strain, which has been used to detect the hybridization of DNA molecules (Fritz et al., Science, 2000). Another surface sensitive technique is the detection of surface plasmons, which is for example realised by the company Biocore.
Semiconductor devices to work as sensors in electrolyte environment such as ion sensitive FETs (ISFETs), mainly fabricated from standard Si substrates but also SOI have been reported and patented (e.g., W00051180). Various techniques have been reported in the field of antibody immobilization (e.g. DE10006760 A) for protein recognition on solid substrates. The first protein chip analog to DNA chips was realized recently (MacBeath G. and Schreiber S L, Science 2000). Cui et al. (Science 2001) demonstrated a functionalized nanostructure for model protein detection, the used Si nanowire however was manufactured in a complicated chemical deposition technique.
A technique directly using the electrical response of sensitive nanostructure devices upon the selective recognition or the detection of membrane proteins or other biomolecules, based on SOI, is not known to the authors.
The techniques currently used mostly suffer from the need to use optical detection. Fluorescent labeling in the case of commercial DNA chips is a rather mature technology. However, it introduces additional biochemical preparation steps, which results in the loss of significant parts of the material of interest. Especially in the labeling of proteins, as much as roughly 50% of the functional protein can be inactivated through the unspecific labeling procedures. This is a major drawback of these approaches, as especially for diagnostic purposes only very small quantities of the analyte are available.
All mentioned techniques based on silicon devices have resolution limits for very small protein concentrations. Proteins of most importance such as certain tumor markers are hardly been detected using the otherwise highly developed 2D electrophoresis technique.